Composition for treating human mental disorders



Patented Nov. 3, 1970 3,538,224 COMPOSITION FOR TREATING HUMAN MENTAL DISORDERS Carl E. Nelson, Ambler, Pa., assignor to Merck & (10., Inc., Rahway, N.J., a corporation of New Jersey No Drawing. Filed Jan. 6, 1969, Ser. No. 789,413 Int. Cl. A61u 27/00 US. Cl. 424-275 7 Claims ABSTRACT OF THE DISCLOSURE Human mental disorders involving depression are treated by the oral administration of a pharmaceutical composition consisting of a combination of protriptyline and chloroprothixene.

This invention relates to pharmaceutical compositions and, more particularly, it relates to novel therapeutic compositions useful in the treatment of human mental disorders involving depression.

The compositions of the present invention are oral dosage forms including as the essential ingredients chloroprothixene or a pharmaceutically acceptable salt thereof and protriptyline or a pharmaceutically acceptable salt thereof. Oral compositions containing such combinations are outstanding in their psycho pharmacological activity.

These mentally depressed disorders are now recognized as among the most distressing of human diseases. The person suffering from one of the many recognized mentally depressed abnormalities presents a serious problem to his associates and family and is often unable to carry on a self-sustaining existence. The disorder may range from a more or less incapacitating depression to a total personality disintegrating condition such as schizophrenia.

Physicians now have available a number of drugs which alleviate these mentally depressed patients so that the person is able to carry on a more satisfying life. But many of the drugs cause side reactions which are disturbing or at least annoying to the patient. One of the most useful drugs employed in the treatment of depression is protriptyline. Although it is extremely useful as an anti-depressant, it also has the eflect of causing heightened anxiety or agitation in certain of the depressed patients. It is now found that with the administration of this highly active anti depressant combined with the known therapeutic agent, chloroprothixene, the agitation and excitement caused by the administration of protriptyline alone is substantially reduced. Thus, the new oral compositions of my invention are extremely useful as new compositions for treating depression and have a wider range of use than previously known agents.

Protriptyline, otherwise known as -(3-methylaminopropyl)-5H-dibenzo[a,d]cycloheptene, is a known material which is useful in the treatment of human patients suffering from mental disorders of depression. Protriptyline and its pharmaceutically acceptable salts are equivalent as far as their pharmacological activity is concerned when used in oral compositions. The preferred form for administration, however, is the hydrochloride salt. The compound chloroprothixene as well as its pharmaceutically acceptable salts are known materials which have been used in the treatment of moderate to severe emotional disorders and especially agitated states associated with neuroses, depression, or schizophrenia.

It has now been found that in accordance with the present invention chloroprothixene and protriptyline combined in therapeutic dosage forms suitable for oral administration exhibit a psycho therapeutic effect which is not possible by the administration of a similar quantity of either of the agents taken by itself.

As indicated above, either of the drugs utilized in the composition of my invention may be in the form of the free base or in the form of a pharmaceutically acceptable salt thereof. The term pharmaceutically acceptable salt when used in conjunction with the chloroprothixene component indicates acid addition salts formed by the reaction of pharmaceutically acceptable acids with the chloroprothixene free base. Typical of the pharmaceutically acceptable acids used in preparing salts of chloroprothixene are hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, and sulfuric acid, or organic acids such as acetic acid, propionic acid, benzoic acid, tartaric acid, lactic acid, maleic acid, citric acid, and the like. The preferred compositions of the invention contain chloroprothixene in the form of the hydrochloride salt.

As indicated above, the protriptyline component, i.e., n-methyl-5H-dibenzo[a,d] cycloheptene 5 propylamine, can be present in the compositions either in the form of a free base or in the form of a pharmaceutically acceptable acid addition salt. The term pharmaceutically acceptable acid addition salt means a salt of the protriptyline free base combined with an equivalent quantity of a pharmaceutically acceptable acid. Here again pharmaceutically acceptable acids comprise mineral acids such as hydrochloric acid, hydrobromic acid, nitric acid, phosphoric acid, and sulfuric acid and the organic acids which are useful include acetic acid, benzoic acid, tartaric acid, lactic acid, maleic acid, and citric acid. The preferred compositions of the invention include protriptyline in the form of the hydrochloride salt. The compositions of ChlOIO prothixene and protriptyline described in the following paragraph are all in the form of the hydrochloride salts.

Compositions of this invention contain the essential active ingredients in a varying ratio so that the physician may select the proper dosage form for administration to the individual patient. Thus, the compositions of my invention are prepared so that a unit dosage form would contain from 5 to 10 mg. of protriptyline and from 10 to 50 mg. of chloroprothixene. These unit dosage forms, including protriptyline and chloroprothixene, are made up in the form of tablets or capsules so that each tablet or capsule will contain 5 to 10 mg. of protriptyline and from 10 to 50 mg. of chloroprothixene. In the event that it is desired to administer the medication in liquid form, a suitable liquid formulation is prepared so that one or two tablespoons of the liquid would convey a combined dosage form of from 5 to 10 mg. of protriptyline along With from 10 to 50 mg. of chloroprothixene. It is of course possible that the two materials may be administered separately, but its is desirable for the effective control of the combined medication that they be admixed prior to use.

The examples which follow will serve to illustrate the invention.

EXAMPLE 1 Per tablet, mg. Protripltyline hydrochloride 5 Chloroprothixene hydrochloride 1O Lactose Starch 21 Magnesium stearate 2 Five gms. of protriptyline, 10 gms. of chloroprothixene, 150 gms. of lactose, and 17 gms. of starch are mixed together. The blended powders are passed through a 40- mesh stainless steel screen to insure uniformity. The mixture is then wet granulated with 40 gms. of a 10% starch paste and sufficient water is added to make a suitable mass. The wetted materials are screened through a No. 12 stainless steel screen, dried overnight at 40 C., and the dried granules are sent through a No. 14 mesh screen. Thereafter, 2 gms. of magnesium stearate is added, blended and compressed into standard tablets, each weighing 200 mg. The tablets are sized with a protective coat of pharmaceutical glaze and sugar-coated in a conventional manner.

EXAMPLE 2 The procedure of Example 1 is followed in detail with the exception that 15 mg. of chloroprothixene rather than 10 is used so that the ratio of protriptyline to chloroprothixene in the individual dose tablets is 5 mg. of protriptyline and 15 mg. of chloroprothixene.

EXAMPLE 3 The procedure of Example 1 is repeated using 25 mg. of chloroprothixene instead of 10 mg. of chloroprothixene so that the individual dose tablet contains a combination of 5 mg. of protriptyline and 25 mg. of chloroprothixene.

EXAMPLE 4 The procedure of Example 1 is repeated using 10 mg. of protriptyline and 50 mg. of chloroprothixene so that the final dose tablet contains 10 mg. of protriptyline-and 50 mg. of chloroprothixene.

EXAMPLE 5 The procedure of Example 1 is repeated using the amounts of 10 mg. of protriptyline and 25 mg. of chloroprothixene so that the unit dosage tablet contains 10 mg. of protriptyline and 25 mg. of chloroprothixene.

The pharmaceutical compositions of this invention are useful for the treatment of (l) acute and chronic states with associated depressed mood, (2) patients with depression in whom anxiety and agitation are severe, and (3) patients with severe anxiety and/r agitation and depressed mood in whom symptoms must be controlled while more definitive diagnostic measures are being undertaken. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate.

EXAMPLE 6 TYPICAL CAPSULE F0 RMULATIONS Per Per capsule, capsule, mg. mg.

Protriptyline hydrochloride 5 Chloroprothixenc 10 10 Lactose 242 Magnesium stearatc 3 Starch, corn 210 Total 260 225 What is claimed:

1. A pharmaceutical compostion in unit dosage form for the treatment of human mental disorders involving depression consisting of a pharmaceutical carrier and as active therapeutic ingredients from 5 to 10 mg. of protriptyline and from 10 to 50 mg. of chloroprothixene.

2. A pharmaceutical composition according to claim 1 containing 5 mg. of protriptyline and 10 mg. of chloroprothixene.

3. A pharmaceutical composition according to claim 1 containing 5 mg. of protriptyline and mg. of chloroprothixene.

4. A pharmaceutical composition according to claim 1 containing 5 mg. of protriptyline and mg. of chloroprothixene.

5. A pharmaceutical composition according to claim 1 containing 10 mg. of protriptyline and mg. of chloroprothixene.

6. A pharmaceutical compoistion according to claim 1 containing 10 mg. of protriptyline and 25 mg. of chloroprothixene.

7. A method of treating patients suffering from mental disorders involving depression which comprises orally administering a pharmaceutical composition consisting of a pharmaceutical carrier and as the active ingredient from 5 to 10 mg. of protriptyline and from 10 to 50 mg. of chloroprothixene.

References Cited Chem. Abst., 63, 12,194b (1965). St.-Jean et al., Current Therapeutic Research, vol. 8, No. 10 (1966), pp. 483-485.

STANLEY J. FRIEDMAN, Primary Examiner US. Cl. X.R. 427-330 

